This is a renewal application for the continued support of the Center of Excellence in Child Health at Washington University School of Medicine. The scientific focus of our Center is to develop and utilize genetic models of human disease states in transgenic and knockout mice and zebrafish. The long term goal of our Center is to develop Scholars in human developmental biology. We shall achieve this goal by applying the recent advances in genome sciences and developmental biology to an understanding of the pathogenesis and treatment of a broad spectrum of diseases within the Pediatric arena. In order to accomplish this, we shall combine the established areas of investigative strength of Washington University School of Medicine and the Department of Pediatrics with genome sciences and developmental biology. Our Scholar's Program, now ten years old, will ultimately close the gap between basic geneticists/genome scientists/developmental biologists and pediatric clinicians. We have in place a structure in which bright, motivated, young pediatric scientists flourish in a protected environment and will emerge as leaders in an evolving area of Pediatrics. Alan L. Schwartz, Ph.D., M.D. will serve as P.I. and Jonathan D. Gitlin, M.D. will serve as Program Director. The Center (via this award and matched funds from Washington University School of Medicine) and its Scholars will continue to utilize our institutionally-funded core facility for the generation of animal models of human disease states via new and evolving state-of-the-art technologies. The long term goals of the Center will be realized as its Scholars contribute to the development of and leadership in human developmental biology during the next two or more decades.